A Single-arm, Open-label Clinical Study Evaluating the Efficacy and Safety of CD20/CD19/CD22 Multi-targeted Chimeric Antigen Receptor T-cell (CAR-T) Injection in Patients With Relapsed/Refractory B-cell Lymphoma.
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 20
- 试验地点
- 4
- 主要终点
- Incidence of Adverse events after CAR-T cells infusion [Safety and Tolerability]
研究概览
简要总结
This is a single-arm, open-label clinical study evaluating the efficacy and safety of CD20/CD19/CD22 multi-targeted chimeric antigen receptor T-cell (CAR-T) injection in patients with relapsed/refractory B-cell lymphoma.
详细描述
The primary objective of this study is to assess the safety and efficacy of CD19/CD20/CD22 muti-target CAR-T therapy in patients with relapsed or refractory B-cell lymphoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary written informed consent obtained from the participant (or legally authorized representative) with good compliance expected throughout the study.
- •All of the following must be fulfilled:
- •Age 2-75 years at the time of informed consent; both sexes eligible.For minors (≤18 years), consent must be provided by a parent or legal guardian; minors who are able to sign must co-sign with their guardian.
- •Histologically confirmed B-cell lymphoma according to the NCCN Clinical Practice Guidelines in Oncology: B-Cell Lymphomas (2024 v3).
- •Relapsed or refractory B-cell lymphoma after at least two prior lines of therapy (one standard chemo-regimen + one salvage regimen) that must have included:
- •anti-CD20 monoclonal antibody (except for subjects with documented CD20-negative tumors), and
- •an anthracycline-containing regimen.
- •Subjects must additionally meet at least one of the following:
- •i. Ineligible for autologous hematopoietic stem-cell transplantation (ASCT); ii. Refusal of ASCT; iii. Relapse after ASCT. d) Disease status at screening:
- •Relapse: progression after prior response (PR or CR).
- •Refractory: i. No response to last therapy (progressive disease [PD] during/after, or best response ≤SD lasting <6 months); OR ii. Relapse or progression after ASCT (biopsy-proven) including: relapse/PD ≤12 months post-ASCT, or relapse/PD after salvage therapy post-ASCT without response (SD or PD).
- •Tumor tissue (archival or fresh biopsy) positive for CD20 and/or CD19 and/or CD22 by immunohistochemistry (pathology report within 6 months preferred).
- •≥1 measurable lesion per Lugano 2014 (Cheson) criteria.
- •ECOG performance status 0-
- •Adequate marrow reserve at screening:Absolute lymphocyte count (ALC) ≥0.3 × 10⁹/L; Platelets ≥30 × 10⁹/L (transfusion permitted).
- •Adequate organ function:AST ≤3×ULN (≤5×ULN if attributable to tumor infiltration); ALT ≤3×ULN (≤5×ULN if attributable to tumor infiltration); Total bilirubin ≤2×ULN (≤3×ULN with direct bilirubin ≤1.5×ULN for Gilbert's syndrome); Serum creatinine ≤1.5×ULN or creatinine clearance ≥60 mL/min (Cockcroft-Gault); Pulmonary reserve: ≤Grade 1 dyspnea and SpO₂ >91 % on room air; LVEF ≥50 % by echocardiography; INR ≤1.5×ULN and APTT ≤1.5×ULN.
- •Women of child-bearing potential must have a negative serum/urine pregnancy test within 7 days before CAR-T infusion. All participants with reproductive potential must use effective contraception from screening through at least 12 months after the last CAR-T dose.
- •Adequate venous access for leukapheresis or repeated phlebotomy, with no contraindications to leukapheresis.
- •Anticipated survival ≥3 months.
排除标准
- •Concurrent malignancy other than the study indication. Exceptions: carcinoma in situ or any malignancy with disease-free survival ≥3 years.
- •Use of immunosuppressive agents or systemic corticosteroids within 1 week before leukapheresis that, in the investigator's judgment, could substantially impair T-cell function.
- •Presence of any of the following:• Positive HBe-Ab and/or HBc-Ab with HBV-DNA above the lower limit of quantification;• Positive HCV-Ab with HCV-RNA above the lower limit of quantification;• Positive Treponema pallidum antibody (TP-Ab);• Positive HIV antibody.
- •Active bacterial, fungal, viral, mycoplasmal, or other infection that, in the investigator's opinion, cannot be adequately controlled.
- •Prior or current CNS disorders unrelated to lymphoma-e.g., seizure disorder, cerebral ischemia/hemorrhage, dementia, cerebellar disease, or any CNS autoimmune disease-deemed uncontrolled by the investigator.
- •Within 12 months before informed consent: percutaneous coronary intervention (angioplasty or stent placement), or NYHA Class III-IV congestive heart failure, or history of myocardial infarction, unstable angina, or other clinically significant cardiac disease judged by the investigator. QTc interval >480 ms (Fridericia correction), or left-ventricular ejection fraction <50 % by echocardiography at screening.
- •Known primary immunodeficiency.
- •History of severe immediate hypersensitivity to any study-related drug.
- •Receipt of any live vaccine within 6 weeks before screening.
- •Pregnant or breastfeeding women.
- •Active autoimmune disease requiring systemic immunosuppressive therapy.
- •Participation in any other interventional clinical trial within 30 days before signing informed consent.
- •Any condition that, in the investigator's opinion, renders the subject unsuitable for study participation.
研究组 & 干预措施
Multi-targeted CAR-T Therapy
Patients will receive a regimen combining CD19/CD22 dual-targeted CAR-T cells with CD19/CD20 dual-targeted CAR-T cells; investigators may administer them sequentially according to each patient's condition.
干预措施: Triple-targeted CAR-T Therapy (Drug)
结局指标
主要结局
Incidence of Adverse events after CAR-T cells infusion [Safety and Tolerability]
时间窗: 28 days post administration of CAR-T-cells
An assessment of severity grade will be made according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
Overall survival (OS)
时间窗: 2 years post CAR T cell infusion
Overall Survival (OS) was defined as the time from the date of first infusion to the date of death due to any cause.
Objective Response Rate (ORR), as assessed by Investigators
时间窗: 2 years post CAR T cell infusion
The Objective Response Rate (ORR) is the percentage of participants who achieved a best overall response of Complete Remission (CR) or Partial Remission (PR)
Duration of response (DOR), as assessed by Investigators
时间窗: 2 years post CAR T cell infusion
Duration of response (DOR) is defined as the time from the first documented objective response to the first documented disease progression or death.
Progression-free survival (PFS), as assessed by Investigators
时间窗: 2 years post CAR T cell infusion
Progression-free survival (PFS) was defined as the time from the date of infusion to the earliest date of the first objective documentation of progressive disease (PD) or death due to any cause.
次要结局
- Pharmacokinetics of CAR-T cells(2 years post CAR T cell infusion)
- Pharmacodynamics of CAR-T cells(2 years post CAR T cell infusion)